International Journal of Molecular Sciences

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16 pages, 3000 KiB

Open AccessArticle

IQGAP3 Is an Important Mediator of Skin Inflammatory Diseases

by Alena Zolotarenko and Sergey Bruskin

Int. J. Mol. Sci. 2024, 25(8), 4545; https://doi.org/10.3390/ijms25084545 - 21 Apr 2024

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Abstract

IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) is member of the IQGAP family of scaffold proteins, which are essential for assembling multiprotein complexes that coordinate various intracellular signaling pathways. Previous research has shown that IQGAP3 is overexpressed in psoriatic skin lesions. Given [...] Read more.

IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) is member of the IQGAP family of scaffold proteins, which are essential for assembling multiprotein complexes that coordinate various intracellular signaling pathways. Previous research has shown that IQGAP3 is overexpressed in psoriatic skin lesions. Given its involvement in processes like cell proliferation and chemokine signaling, we sought to explore its molecular role in driving the psoriatic phenotype of keratinocytes. By conducting transcriptome profiling of HaCaT keratinocytes, we identified numerous psoriasis-associated pathways that were affected when IQGAP3 was knocked down. These included alterations in NFkB signaling, EGFR signaling, activation of p38/MAPK and ERK1/ERK2, lipid metabolism, cytokine production, and the response to inflammatory cytokine stimulation. Real-time analysis further revealed changes in cell growth dynamics, including proliferation and wound healing. The balance between cell proliferation and apoptosis was altered, as were skin barrier functions and the production of IL-6 and IFNγ. Despite these significant findings, the diversity of the alterations observed in the knockdown cells led us to conclude that IQGAP3 may not be the best target for the therapeutic inhibition to normalize the phenotype of keratinocytes in psoriasis. Full article

(This article belongs to the Special Issue Recent Advances of Proteomics in Human Health and Disease)

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23 pages, 8253 KiB

Open AccessArticle

Exploring the Molecular Tapestry: Organ-Specific Peptide and Protein Ultrafiltrates and Their Role in Therapeutics

by Jakub Peter Slivka, Chris Bauer, Alexander Younsi, Michelle B. F. Wong, Mike K. S. Chan and Thomas Skutella

Int. J. Mol. Sci. 2024, 25(5), 2863; https://doi.org/10.3390/ijms25052863 - 1 Mar 2024

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Abstract

This study aims to characterize the proteome composition of organ-derived protein extracts from rabbits. Protein isolation was performed using soft homogenization and size exclusion via ultrafiltration. The proteome analysis of the ultrafiltrates was conducted using gel electrophoresis, and the mass spectrometry data were [...] Read more.

This study aims to characterize the proteome composition of organ-derived protein extracts from rabbits. Protein isolation was performed using soft homogenization and size exclusion via ultrafiltration. The proteome analysis of the ultrafiltrates was conducted using gel electrophoresis, and the mass spectrometry data were subjected to gene ontology analysis. Proteomic profiling revealed comprehensive protein profiles associated with RNA regulation, fatty acid binding, inflammatory response, oxidative stress, and metabolism. Additionally, our results demonstrate the presence of abundant small proteins, as observed in the mass spectrometry datasets. Small proteins and peptides are crucial in transcription modulation and various biological processes. The protein networks identified in the ultrafiltrates have the potential to enhance and complement biological therapeutic interventions. Data are available via ProteomeXchange with identifier PXD050039. Full article

(This article belongs to the Special Issue Recent Advances of Proteomics in Human Health and Disease)

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Review

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17 pages, 1363 KiB

Open AccessReview

Low-Abundance Protein Enrichment for Medical Applications: The Involvement of Combinatorial Peptide Library Technique

by Egisto Boschetti and Pier Giorgio Righetti

Int. J. Mol. Sci. 2023, 24(12), 10329; https://doi.org/10.3390/ijms241210329 - 19 Jun 2023

Cited by 3 | Viewed by 1460

Abstract

The discovery of low- and very low-abundance proteins in medical applications is considered a key success factor in various important domains. To reach this category of proteins, it is essential to adopt procedures consisting of the selective enrichment of species that are present [...] Read more.

The discovery of low- and very low-abundance proteins in medical applications is considered a key success factor in various important domains. To reach this category of proteins, it is essential to adopt procedures consisting of the selective enrichment of species that are present at extremely low concentrations. In the past few years pathways towards this objective have been proposed. In this review, a general landscape of the enrichment technology situation is made first with the presentation and the use of combinatorial peptide libraries. Then, a description of this peculiar technology for the identification of early-stage biomarkers for well-known pathologies with concrete examples is given. In another field of medical applications, the determination of host cell protein traces potentially present in recombinant therapeutic proteins, such as antibodies, is discussed along with their potentially deleterious effects on the health of patients on the one hand, and on the stability of these biodrugs on the other hand. Various additional applications of medical interest are disclosed for biological fluids investigations where the target proteins are present at very low concentrations (e.g., protein allergens). Full article

(This article belongs to the Special Issue Recent Advances of Proteomics in Human Health and Disease)

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